Antidiabetic role of a novel protein from garlic via NO in expression of Glut-4/insulin in liver of alloxan induced diabetic mice

• Published in: Biomedicine & pharmacotherapy 2019-03, Vol.111, p.1302-1314
• Main Authors: Bhattacharya, Suman, Maji, Uttam, Khan, Gausal A., Das, Rahul, Sinha, Asru K., Ghosh, Chandradipa, Maiti, Smarajit
• Format: Article
• Language: English
• Subjects: Alloxan - pharmacology; Animals; Aqueous extract of garlic; Blood Glucose - drug effects; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Garlic - chemistry; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; Glut-4; Hepatocytes - drug effects; Hepatocytes - metabolism; Hyperglycemia - drug therapy; Hyperglycemia - metabolism; Hypoglycemic Agents - pharmacology; Insulin; Insulin - metabolism; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Liver; Liver - drug effects; Liver - metabolism; Mice; Nitric Oxide - metabolism; Nitric oxide synthase; Plant Extracts - pharmacology
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.01.036

Garlic has been reported to stimulate nitric-oxide (NO) synthesis in various cells. The role of aqueous-extract of garlic (AEG) and a purified NO-generating protein from garlic (NGPG) was investigated to control hyperglycemia by hepatic insulin synthesis through NGPG induced synthesis of NO via glucose-activated NO-synthase and glucose transporter-4 (Glut-4) in the hepatocytes. Type-1-diabetic mellitus mice were prepared by alloxan treatment, NO was determined by methemoglobin method, insulin synthesis was quantitated by ELISA. TNF-α and NFκβ was quantitated by ELISA. The AEG-induced Glut-4 synthesis was determined by in-vitro translation of mRNA from the hepatocytes. The NO-generating protein from AEG was purified to homogeneity by chromatography on DEAE-cellulose and Sephadex G-50 columns and sequenced/characterized by Mass-spectral-analysis. Purified NGPG injection to diabetic mice significantly reduced the blood-sugar and increase insulin level in diabetic animal. It also increases insulin-release, Glut-4 synthesis, glucose-uptake in both liver and β-cells of diabetic mice. NGPG down regulated pro-inflammatory cytokine TNF-α and the stress responsive NFκB-expression in liver cell of diabetic mice. Injection of AEG to the diabetic mice reduced the blood glucose level from 550 ± 10 mg/dL to 125 ± 10 mg/dL in 16 h with simultaneous increase of plasma NO from 0 nmol/h to 2.5 nmol/h and insulin 2 ± 1.1μunit/mL to 15μunit/mL at 16 h. Oral administration of AEG to adult diabetic mice increased NO, insulin and Glut-4 synthesis in the hepatocytes. AEG and the purified-NGPG protein can control hyperglycemia through the stimulation of NO by glucose-activated NO-synthase that would play an important role in the synthesis of insulin/Glut-4 in liver-cells.